Page 1869 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 108 Graft-Versus-Host Disease and Graft-Versus-Leukemia Responses 1661

TABLE Commonly Administered Drugs for Graft-Versus-Host Disease Prophylaxis and Treatment
108.4
Drug Mechanism Adverse Effects
Corticosteroids Direct lymphocyte toxicity; suppress Hyperglycemia, acute psychosis, severe myopathy, neuropathy,
proinflammatory cytokines such as TNF-α osteoporosis, cataract development
Methotrexate (MTX) Antimetabolite: inhibit T-cell proliferation Significant renal, hepatic, and gastrointestinal toxicities
2+
Cyclosporine A (CSA) IL-2 suppressor; blocks Ca -dependent signal Renal and hepatic insufficiency, hypertension, hyperglycemia, headache,
transduction distal to TCR engagement nausea and vomiting, hirsutism, gum hypertrophy, seizure with severe
toxicity
Tacrolimus (FK506) IL-2 receptor; blocks Ca -dependent signal Similar to CSA
2+
transduction distal to TCR engagement
Mycophenolate mofetil (MMF) Inhibits de novo purine synthesis Body aches, abdominal pain, nausea and vomiting, diarrhea,
neutropenia
Sirolimus mTOR inhibitor Thrombocytopenia, hyperlipidemia, TTP
Antithymocyte globulin (ATG) Polyclonal immunoglobulin Anaphylaxis, serum sickness
IL-2, Interleukin-2; mTOR, mammalian target of rapamycin; TCR, T-cell receptor; TNF-α, tumor necrosis factor-α; TTP, thrombotic thrombocytopenic purpura.

affected by chronic GVHD. Destruction of sweat glands can cause Pulmonary
hyperthermia. 343
Bronchiolitis obliterans is a late and serious manifestation of chronic
343
GVHD. Patients typically present with a cough or dyspnea. Severe
Ocular sclerotic disease of the chest wall may also give rise to similar symp-
toms with no intrinsic pulmonary disease. Pulmonary function tests
Ocular GVHD usually presents with xerophthalmia or dry eyes. demonstrate obstructive physiology and a reduction in DLCO. Chest
Irreversible destruction of the lacrimal glands results in dryness, computed tomography results may be normal or may show hyperin-
photophobia, and burning. Local therapy with preservative-free tears flation with a ground-glass appearance. Overall, patients with bron-
and ointment or the placement of punctal plugs by an ophthalmolo- chiolitis obliterans have minimal response to therapy and a very poor
gist might be required. Conjunctival GVHD, a rare manifestation of prognosis. Patients with chronic GVHD are also at risk for chronic
severe chronic GVHD, has a poor prognosis. 24,343 sinopulmonary infections, but symptoms may be minimal. 24

Oral Hematopoietic

343
Oral GVHD causes xerostomia and/or food sensitivity. More Cytopenias in chronic GVHD are common. This may be a result of
advanced disease may cause odynophagia caused by esophageal stromal damage, but autoimmune neutropenia, anemia, and/or
damage and strictures, although esophageal involvement occurs rarely thrombocytopenia are also seen. Thrombocytopenia at the time of
without oral disease. Physical examination may reveal only erythema chronic GVHD diagnosis is associated with poor prognosis. However,
with a few white plaques, prompting a misdiagnosis of thrush or thrombocytopenia posttransplant is a poor prognostic factor regard-
herpetic infections. Lichenoid changes in advanced disease can cause less of GVHD, and eosinophilia is occasionally seen with chronic
extensive plaque formation. 24 GVHD.

Gastrointestinal Immunologic

Patients with chronic GVHD have GI complaints that mimic other Chronic GVHD is inherently immunosuppressive. Functional
disease states, including acute GVHD, infection, dysmotility, lactose asplenia with an increased susceptibility to encapsulated bacteria is
intolerance, pancreatic insufficiency, and drug-related side effects. In common, and circulating Howell-Jolly bodies can be seen on periph-
one retrospective review of the intestinal biopsies of patients with eral blood smear. Patients are also at risk for invasive fungal infections
chronic GVHD and persistent GI symptoms, a majority of patients and Pneumocystis carinii pneumonia. Hypoglobulinemia is common,
had evidence of both acute and chronic GVHD, and only 7% of and patients with levels below 500 mg/dL should be supplemented
the patients had isolated chronic GVHD. 24,336 Thus although with intravenous immunoglobulin.
chronic GVHD may involve the GI tract alone, it may be difficult
to diagnose in those circumstances without concurrent acute
GVHD. Musculoskeletal

Fascial involvement in sclerodermatous GVHD is usually associated
Hepatic with skin changes. Fasciitis in joint areas can cause severe restriction of
range of motion. Muscle cramps are a common complaint in patients
Hepatic disease typically presents as cholestasis with elevated serum with chronic GVHD, but myositis with elevated muscle enzymes is
levels of alkaline phosphatase and bilirubin. Isolated hepatic chronic rare. Many patients with chronic GVHD are on steroid therapy and
GVHD has become more common with the increasing use of donor have low levels of sex hormone posttransplant. Thus avascular necrosis,
11
lymphocyte infusions. Liver biopsy is required to confirm the osteopenia, and osteoporosis are frequent complications.
diagnosis of chronic hepatic GVHD in patients with no other target Although several cases have been described, it is yet to be deter-
organ involvement. mined in large studies whether kidneys, which are primary targets in